Pharmacokinetic evaluation of recombinant, activated factor VII in patients with inherited factor VII deficiency

Background and Objectives. Recombinant factor VIIa (rFVIIa) has been widely used in the treatment of bleedings occurring in hemophiliacs with inhibito rs. Very few reports exist on the use of rFVIIa in patients with inherited FVII deficiency. Pharmacokinetic studies on rFVIIa have been performed excl usively in hemophiliacs, patients with cirrhosis or volunteers pretreated w ith acenocoumarol, The aim of this study was to evaluate the kinetics of rF VIIa in patients naturally deficient of FVII. Design and Methods. A single dose kinetic study with rFVIIa was performed i n 5 patients affected by severe congenital deficiency of factor VII in orde r to evaluate the true kinetic parameters of rFVIIa without the interferenc e of FVII. Two dosages, 15 and 30 mug/kg, were used in a crossover schedule . FVII:C and FVIIa concentration/time curves were analyzed by a model-indep endent method. Antithrombin (AT), prothombin fragment 1+2 (F1+2) and tissue factor pathway inhibitor (TFPI) were assayed. Results. No differences emerged between the dosages with respect to dose-in dependent parameters [total body clearance (CL), volume of distribution are a (VdArea), mean residence time (MRT)]. No significant changes of AT,TFPI, and F1+2 were observed. Comparing the results with those of other studies p erformed in adult hemophiliacs, in patients affected by cirrhosis or in vol unteers on oral anticoagulant therapy (OAT), Ct and VdArea of rFVIIa were d efinitely higher and in vivo recovery was lower. Interpretation and Conclusions. These findings suggest that the kinetics of rFVIIa are not dose-dependent. In the absence of FVII, the changes of VdAr ea and Ct may be in agreement with a mechanism of competition between MI an d rFVIIa for tissue factor binding. (C) 2001, Ferrata Storti Foundation.